Pliability in the m6A-Binding Region Extends Druggability of YTH Domains.
J Chem Inf Model
; 64(5): 1682-1690, 2024 03 11.
Article
em En
| MEDLINE
| ID: mdl-38417111
ABSTRACT
Epitranscriptomic mRNA modifications affect gene expression, with their altered balance detected in various cancers. YTHDF proteins contain the YTH reader domain recognizing the m6A mark on mRNA and represent valuable drug targets. Crystallographic structures have been determined for all three family members; however, discrepancies are present in the organization of the m6A-binding pocket. Here, we present new crystallographic structures of the YTH domain of YTHDF1, accompanied by computational studies, showing that this domain can exist in different stable conformations separated by a significant energetic barrier. During the transition, additional conformations are explored, with peculiar druggable pockets appearing and offering new opportunities for the design of YTH-interfering small molecules.
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1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação a RNA
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article